Biology subjects

Bertocchini, F.

Publications and source records attributed to Bertocchini, F..

7 recordsLinked to original sources

bioRxiv2025

Metabolic overflow prevents ecological collapse in microbial populations

Metabolic overflow is defined by the excretion of partially oxidized byproducts, such as acetate, ethanol, and lactate, which could otherwise be used to produce energy. This behavior, widespread across diverse biological systems, is paradoxical because it suggests a seemingly wasteful use of resources that could instead be employed to maximize energy production. In this work, we investigate the ecological implications of metabolic overflow, using bacterial acetate metabolism as a model. We formulate a second-order generalization of the logistic growth equation, incorporating resource availability and acceleration dynamics to provide an explicit mechanistic link between metabolic overflow and ecological collapse. We demonstrate that acetate-mediated growth deceleration reduces the risk of overshoot and collapse, especially under conditions of resource oversupply. By inhibiting excessive proliferation, acetate overflow enhances the survival and stability of bacterial communities in fluctuating environments. In this context, acetate acts as a quorum-sensing signal, coordinating population-wide responses and enabling the active regulation of growth rates before resource exhaustion occurs. Our findings suggest that overflow metabolism is an adaptive strategy evolved to mitigate the risk of ecological collapse and stabilize microbial populations. These insights highlight the dual role of metabolic byproducts as both inhibitors of growth and regulators of population dynamics, with significant implications for microbial ecology and biotechnological applications.

ecology↗

bioRxiv2024

A functional approach to homeostatic regulation

In this work, we present a novel modeling framework for understanding the dynamics of homeostatic regulation. Inspired by engineering control theory, this framework incorporates unique features of biological systems. First, biological variables often play physiological roles, and taking this functional context into consideration is essential to fully understand the goals and constraints of homeostatic regulation. Second, biological signals are not abstract variables, but rather material molecules that may undergo complex turnover processes of synthesis and degradation. We suggest that the particular nature of biological signals may condition the type of information they can convey, and their potential role in shaping the dynamics and the ultimate purpose of homeostatic systems. We show that the dynamic interplay between regulated variables and control signals is a key determinant of biological homeostasis, challenging the necessity and the convenience of strictly extrapolating concepts from engineering control theory in modeling the dynamics of homeostatic systems. This work provides an alternative, unified framework for studying biological regulation and identifies general principles that transcend molecular details of particular homeostatic mechanisms. We show how this approach can be naturally applied to apparently different regulatory systems, contributing to a deeper understanding of homeostasis as a fundamental process in living systems.

physiology↗

bioRxiv2024

Redefining the role of Hypoxia-inducible factors (HIFs) in oxygen homeostasis

Hypoxia-inducible factors (HIFs) are key regulators of intracellular oxygen homeostasis. The marked increase in HIFs activity in hypoxia as compared to normoxia, together with their transcriptional control of primary metabolic pathways, motivated the widespread view of HIFs as responsible for the cells metabolic adaptation to hypoxic stress. In this work, we suggest that this prevailing model of HIFs regulation is misleading. We propose an alternative model focused on understanding the dynamics of HIFs activity within its physiological context. Our model suggests that HIFs would not respond to but rather prevent the onset of hypoxic stress by regulating the traffic of electrons between catabolic substrates and oxygen. The explanatory power of our approach is patent in its interpretation of the Warburg effect, the tendency of tumor cells to favor anaerobic metabolism over respiration, even in fully aerobic conditions. This puzzling behavior is currently considered as an anomalous metabolic deviation. Our model predicts the Warburg effect as the expected homeostatic response of tumor cells to the abnormal increase in metabolic demand that characterizes malignant phenotypes. This alternative perspective prompts a redefinition of HIFs function and underscores the need to explicitly consider the cells metabolic activity in understanding its responses to changes in oxygen availability.

cell biology↗

bioRxiv2023

Killing them softly with EPO: a new role for erythropoietin in the homeostasis of red blood cells

The regulation of red blood cell (RBC) homeostasis is widely assumed to rely on the control of cell production by erythropoietin (EPO) and the destruction of cells at a fixed, species-specific age. In this work, we show that such a regulatory mechanism is a poor homeostatic solution to satisfy the changing needs of the body. Effective homeostatic control requires RBC lifespan to be variable and tightly regulated. We show that EPO controls RBC lifespan by determining CD47 expression in newly formed RBCs and SIRP- expression in sinusoidal macrophages. EPO also controls the initiation and intensity of anti-RBC autoimmune responses that curtail RBC lifespan in some circumstances. These mechanisms continuously modulate the rate of RBC destruction depending on oxygen availability. The finding of new homeostatic roles for EPO and autoimmunity critically challenges the current paradigm of RBC homeostasis and sets the grounds for a new approach to this field.

physiology↗

bioRxiv2022

The coordination of innate and adaptive immunity in bacteria

Bacteria have evolved a variety of innate and adaptive immune strategies to fight bacteriophage (phage) infections. Innate defenses (unspecific mechanisms directed against any phage infecting the cell) range from the identification and cleavage of the viral DNA by restriction nucleases to the suicidal death of infected host cells, an extreme solution that prevents the spread of the infection throughout the population. Adaptive immunity, on the other hand, involves the creation of an immune memory that targets specific phages in case of reinfection. It is obvious that not every infection leads to the suicide of the host cell or to the formation of immune memory against the infecting phage, so what determines the outcome of an anti-phage response? In this work, we suggest that the dynamic aspects of phage infections are key to addressing this question. We show that the rates of viral DNA replication and cleavage define functional categories of phages that differ in their susceptibility to the immune strategies evolved by bacteria. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. This perspective allows us to formulate simple molecular mechanisms that could account for the decision of infected cells to undergo suicidal cell death or to incorporate new phages into the immune memory. This work highlights the importance of dynamics to understand bacterial immunity and formulates explicit hypotheses that could inspire a new and original empirical approach to the study of phage/bacteria interactions.

microbiology↗

bioRxiv2022

The virtualome: a computational framework toevaluate microbiome analyses

Microbiomes have been the focus of a substantial research effort in the last decades. The composition of microbial populations is normally determined by comparing DNA sequences sampled from those populations with the sequences stored in genomic databases. Therefore, the amount of information available in databanks should be expected to constrain the accuracy of microbiome analyses. Albeit normally ignored in microbiome studies, this constraint could severely compromise the reliability of microbiome data. To test this hypothesis, we generated virtualomes, virtual bacterial populations that exhibit the ecological structure of real-world microbiomes. Confronting the analyses of virtualomes with their original composition revealed critical issues in the current approach to characterizing microbiomes, issues that were empirically confirmed by analyzing the microbiome of Galleria mellonella larvae. To reduce the uncertainty of microbiome data, the effort in the field must be channeled towards significantly increasing the amount of available genomic information.

bioinformatics↗

bioRxiv2022

Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella

Plastic degradation by biological systems with re-utilization of the by-products can be the future solution to the global threat of plastic waste accumulation. We report that the saliva of Galleria mellonella larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours exposure at room temperature and physiological conditions (neutral pH). The wax worm saliva can indeed overcome the bottleneck step in PE biodegradation, that is the initial oxidation step. Within the saliva, we identified two enzymes that can reproduce the same effect. This is the first report of enzymes with this capability, opening up the way to new ground-breaking solutions for plastic waste management through bio-recycling/up-cycling.

molecular biology↗